COX-2 has an established role in postnatal kidney development. 15-hydroxyprostaglandin dehydrogenase (15-PGDH) is recently identified as an endogenous inhibitor of COX-2, limiting the production of COX-2-derived prostanoids in several pathological conditions. The present study was undertaken to examine the regulation of renal 15-PGDH expression during postnatal kidney development in rats, in comparison with COX-2. qRT-PCR and immunoblotting demonstrated that 15-PGDH mRNA and protein in the kidney were present in neonates, peaked in the 2nd postnatal weeks, and then declined sharply to very low level in adulthood. Immunostaining demonstrated that at the 2nd postnatal week, renal 15-PGDH protein was predominantly found in the proximal tubule stained positive for NHE3 whereas COX-2 protein was restricted to macular densa and adjacent thick ascending limbs stained positive for AQP2. Interestingly, in the 4th week of postnatal week, 15-PGDH protein was redistributed to thick ascending limbs stained positive for NKCC2. After 6 weeks of age, 15-PGDH protein was found in the granules in subsets of the proximal tubule. Overall, these results support a possibility that 15-PGDH may regulate postnatal kidney development through interaction with COX-2.